This proposal is concerned with extending our understanding of the mechanism by which asparaginase exerts its antitumor effect and investigating other enzymes with potential as tumor inhibitory agents. The effect of both tumor inhibitory and non-inhibitory asparaginases on asparagine levels in blood, normal tissue and tumors will be determined. Biologic half-life and kinetic parameters will be measured for these same preparations. In this way, there may be developed a catalogue of properties for asparaginases from which to seek correlations with antitumor activity and thereby delineate the more critical factors for good inhibition of tumor growth. Immunosuppression, another interesting aspect of asparaginase activity, is most potent when enzyme is administered simultaneously with or shortly after antigen. This finding suggests that during the inductive phase of the immune response, asparagine is required for synthesis of a substance essential for lymphocyte transformation. An attempt will be made to find such a substance. Attention will be directed to L-serine dehydratase as a potential tumor inhibitory enzyme. Serine dehydratases from various sources will be prepared and screened for anti-tumor activity. Other enzymes will also be examined as the studies progress.